Presynaptic neurones may contribute a unique glycoprotein to the extracellular matrix at the synapse

As the extracellular matrix at the original site of a neuromuscular junction seems to play a major part in the specificity of synaptic regeneration, considerable attention has been paid to unique molecules localized to this region. Here we describe an extracellular matrix glycoprotein of the elasmobranch electric organ that is localized near the nerve endings. By immunological criteria, it is synthesized in the cell bodies, transported down the axons and is related to a glycoprotein in the synaptic vesicles of the neurones that innervate the electric organ. It is apparently specific for these neurones, as it cannot be detected elsewhere in the nervous system of the fish. Therefore, neurones seem to contribute unique extracellular matrix glycoproteins to the synaptic region. Synaptic vesicles could be involved in transporting these glycoproteins to or from the nerve terminal surface.     

p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development

The p63 gene, a homologue of the tumour-suppressor p53, is highly expressed in the basal or progenitor layers of many epithelial tissues. Here we report that mice homozygous for a disrupted p63 gene have major defects in their limb, craniofacial and epithelial development. p63 is expressed in the ectodermal surfaces of the limb buds, branchial arches and epidermal appendages, which are all sites of reciprocal signalling that direct morphogenetic patterning of the underlying mesoderm. The limb truncations are due to a failure to maintain the apical ectodermal ridge, a stratified epithelium, essential for limb development. The embryonic epidermis of p63-/- mice undergoes an unusual process of non-regenerative differentiation, culminating in a striking absence of all squamous epithelia and their derivatives, including mammary, lacrymal and salivary glands. Taken together, our results indicate that p63 is critical for maintaining the progenitor-cell populations that are necessary to sustain epithelial development and morphogenesis.     

Break—even Analyses for Random production and Demand Processes

Break-even analyses are often used as controlling instruments. Typically, they are applied to support decision processes or to gain information for the control of profits and sales. Firstly, the study gives an overview of the basic accounting systems. Secondly, the study shows possible ways of performing breakeven analyses for a single-stage, make-to-order production in the case of random production and demand structures. To model these structures, queueing systems are employed. As a general result, we see that break-even analyses must always be performed taking into account an existing planning system. Under practical aspects, GI/G/1 systems turn out to map complex real situations realistically. From the examples given it can be concluded that one achieves different results compared with using a deterministic model even in the case of a simple, random effects approach. In particular it is shown that stochastic modelling in general is helpful in avoiding incorrect decisions.     

Arachidonic acid metabolites as mediators of somatostatin-induced increase of neuronal M-current

The M-current (IM) is a time- and voltage-dependent K+ current that persists at slightly depolarized membrane potentials. IM is reduced by muscarinic cholinergic agonists and certain peptides, and is thought to be responsible in part for the slow and late slow excitatory postsynaptic potentials in sympathetic neurons. Recently, we reported that IM in hippocampal neurons was also augmented by somatostatin-14 and -28 suggesting that two different receptors reciprocally regulate one neuronal channel type. Muscarinic effects on IM may be mediated by various components of the phosphatidylinositol phosphate pathway. We now report the involvement of a different second messenger pathway, that generated by phospholipase A2, in the somatostatin-induced augmentation of IM in hippocampal cells. This pathway generates arachidonic acid from which leukotrienes can be produced by lipoxygenases. We find that the IM-augmenting effects of somatostatin are abolished by two substances that can inhibit phospholipase A2, quinacrine and 4-bromophenacyl bromide, and that both arachidonic acid and leukotriene C4 mimic the effects of somatostatin-14 on hippocampal pyramidal neurons in vitro. Arachidonic and somatostatin effects are blocked by a lipoxygenase inhibitor, implicating an arachidonic acid metabolite, perhaps a leukotriene, in the somatostatin effect.     

日益增长的城市问题

城市增长是二十一世纪人类最大的挑战之一。根据目前的预测,全世界的城市人口每年增长大约五千万。这种增长几乎是指数式的,在本世纪中期就可能达到饱和。因此就有了很多讨论和评估,关于土地消耗、特大城市可管理的面积以及组织而非控制这种快速传播的城市化的简单方法。为此,更好地理解城市增长的空间动力学应该是一个先决条件。实际上,城市规划学、城市地理学、城市经济学以及其它的相关学科已经在这个问题上作了很大的努力。虽然它们对一些细节有了深入研究,但是没有提出蕴含在这些复杂动力学下面的总的机制的大框图。因此有理由考虑是否…     

Guaiacol-O-methyltransferase: A mammalian enzyme capable of forming di-O-methyl catecholamine derivatives

Résumé On a extrait et characterisé une enzyme capable de transférer aux catécholamines 4-O-méthyles le group méthyle provenant de l'S-adénosylméthionine et produire des substances diméthoxyques. Cette enzyme est active dans différents tissus de Mammifères.

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This work was supported by Public Health Service grants Nos. MH-08618 and MH-07961 and a Research Scientist's Award No. MH-14020, to A.J.F.     

Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death

Huntington's disease is caused by an abnormal polyglutamine expansion within the protein huntingtin and is characterized by microscopic inclusion bodies of aggregated huntingtin and by the death of selected types of neuron. Whether inclusion bodies are pathogenic, incidental or a beneficial coping response is controversial. To resolve this issue we have developed an automated microscope that returns to precisely the same neuron after arbitrary intervals, even after cells have been removed from the microscope stage. Here we show, by survival analysis, that neurons die in a time-independent fashion but one that is dependent on mutant huntingtin dose and polyglutamine expansion; many neurons die without forming an inclusion body. Rather, the amount of diffuse intracellular huntingtin predicts whether and when inclusion body formation or death will occur. Surprisingly, inclusion body formation predicts improved survival and leads to decreased levels of mutant huntingtin elsewhere in a neuron. Thus, inclusion body formation can function as a coping response to toxic mutant huntingtin.